Idelalisib (Zydelig) is a small-molecule kinase inhibitor that is used in combination with rituximab to treat hematological malignancies such as CLL and non-Hodgkin lymphoma.
Idelalisib Uses:
-
Chronic lymphocytic leukemia:
-
- Medication for worsened constant lymphocytic leukemia (CLL) (in combination with rituximab) when rituximab alone is suitable treatment due to other comorbidities.
-
-
Follicular B-cell non-Hodgkin lymphoma:
-
- Treatment of relapsed follicular B-cell non-Hodgkin lymphoma (NHL) after at least 2 earlier systemic therapies
-
-
Small lymphocytic lymphoma:
- Treatment of relapsed small lymphocytic lymphoma (SLL) after at least 2 earlier systemic treatments.
- Limitations of use: Idelalisib is not recommended for first-line treatment of CLL, follicular B-cell NHL, or SLL. Idelalisib is not recommended in combination with bendamustine and/or rituximab for the treatment of follicular NHL.
Idelalisib (Zydelig) Dose in Adults:
Note: The maximum suggested initial dose is 150 mg two times every day. The ideal duration and safety of therapy beyond several months is presently unidentified.
Idelalisib (Zydelig) Dose in the treatment of relapsed chronic lymphocytic leukemia:
- Oral: 150 mg two times each day (in combination with rituximab); continue until disease progression or undesirable toxicity.
Idelalisib (Zydelig) Dose in the treatment of relapsed follicular B-cell non-Hodgkin lymphoma:
- Oral: 150 mg two times each day; continue until disease progression or unacceptable toxicity.
Idelalisib (Zydelig) Dose in the treatment of relapsed small lymphocytic lymphoma:
- Oral: 150 mg two times each day; continue until disease progression or unacceptable toxicity.
Use in Children:
Not indicated.
Pregnancy Risk Category: D
- Based on animal reproductive studies and the action process, idelalisib can cause harm to the foetus if administered during pregnancy.
- Before starting treatment with idelalisib, make sure you have checked for pregnancy in women of reproductive potential.
- Effective contraception must be used by females with reproductive potential throughout treatment and at least one month after the last idelalisib dosage.
- Effective contraception should be used by males who have female partners with reproductive potential throughout treatment and for three months after the last idelalisib dose.
Use of Idelalisib while breastfeeding
- It isn't known if breast milk contains idelalisib.
- The manufacturer suggests that breastfeeding be stopped during treatment, and at least for one month after the last dose of idelalisib.
Dose in Kidney Disease:
- CrCl ≥15 mL/minute:
- No dosage modifications required.
- CrCl <15 mL/minute:
- There are no dosage modifications given in the manufacturer’s labeling (it has not been studied).
Idelalisib (Zydelig) Dose in Liver disease:
-
Preexisting hepatic impairment:
- Based on a pharmacokinetic study in patients with mild and serious hepatic damage (Child-Pugh classes B and C) as compared to healthy people, single oral doses of 150 mg were tolerated well; idelalisib and GS-563117 exposure discrepancies were observed but not deemed clinically significant.
- ALT or AST or bilirubin higher than the ULN: Dosage adjustment is not needed. However, limited safety data are available in patients with baseline ALT or AST >2.5 times ULN or bilirubin >1.5 times ULN. Watch carefully for toxicity.
-
Hepatotoxicity during treatment:
- ALT/AST >3 to 5 times ULN or bilirubin >1.5 to 3 times ULN:
- Continue present dose; examine LFTs at least weekly until ALT/AST and/or bilirubin ≤1 times ULN.
- ALT/AST >5 to 20 times ULN or bilirubin >3 to 10 times ULN:
- momentarily interrupt treatment. Monitor LFTs at least weekly until ALT/AST and/or bilirubin ≤1 times ULN, then may restart treatment at 100 mg two times every day.
- ALT/AST >20 times ULN or bilirubin >10 times ULN:
- Terminate permanently.
- ALT/AST >3 to 5 times ULN or bilirubin >1.5 to 3 times ULN:
Common Side Effects of Idelalisib (Zydelig):
-
Central Nervous System:
- Fatigue
- Insomnia
- Headache
-
Dermatologic:
- Skin Rash
- Night Sweats
-
Gastrointestinal:
- Diarrhea
- Nausea
- Abdominal Pain
- Decreased Appetite
- Vomiting
-
Hematologic & Oncologic:
- Decreased Hemoglobin
- Decreased Platelet Count
- Neutropenia
-
Hepatic:
- Increased Serum ALT
- Increased Serum AST
- Severe Hepatotoxicity
-
Infection:
- Severe Infection
-
Neuromuscular & Skeletal:
- Weakness
-
Respiratory:
- Cough
- Pneumonia
- Dyspnea
- Upper Respiratory Tract Infection
-
Miscellaneous:
- Fever
Less Common Side Effects of Idelalisib (Zydelig):
-
Cardiovascular:
- Peripheral edema
-
Respiratory:
- Pneumonitis
Contraindications to Idelalisib (Zydelig):
- Severe allergic reactions to idelalisib and any component of the formulation, including anaphylaxis or toxic epidermal necrlysis.
Canadian labeling: Additional contraindications not in the US labeling
- It is used in the treatment of chronic lymphocytic and non-Hodgkin's lymphoma patients.
Warnings and precautions
-
Suppression of bone marrow
- It is common to experience grade 3 or 4 neutropenia; thrombocytopenia (any grade) and anemia have also been reported.
- For the first 6 months, blood counts should be checked at least once every 14 days. Patients with neutropenia should be checked at least weekly (ANC 1,000/mm3).
- You may need to pause treatment and reduce dosage.
- Dosage modification is not required for lymphocytosis.
-
Dermatologic toxicities:
- Some cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported, some fatal.
- There have been cases of severe and/or life-threatening dermal/mucocutaneous reactions, including exfoliative dermatitis (generalized, generalized, erythematous and maculopapular papular, papular and exfoliative) and skin disease.
- Examine your skin for signs of dermatologic toxicity. If you find any, report it immediately.
-
Gastrointestinal events [US Boxed Warning]
- Perforation of the intestinal tract can be fatal and serious. If this happens, discontinue idelalisib immediately.
- Perforation in some patients was caused by mild to severe diarrhea.
- Colitis and diarrhea have been reported when single-agent idelalisib is used with rituximab.
- Examine carefully for any new or worsening abdominal pains, chills or fevers.
-
Hepatotoxicity: [US Boxed Warning]
- It has been reported that some people have severe hepatotoxicity.
- Monitor your liver function during treatment and at baseline.
- It is possible to have treatment interrupted, reduced dosage, or discontinued.
- When single-agent idelalisib is used in combination with Rituximab and unapproved combination treatments, hepatotoxicity has been reported.
- Transaminase elevations of >5 times the ULN were observed and commented on during the first three months.
- Therapy was terminated after transaminase elevations were reversed.
- Recurrent hepatotoxicity can occur even with a reduced dose. Stop using this medication.
- Use it only with other hepatotoxic drugs.
- At baseline, examine ALT/AST every 14 days for the first 12 week, every 4 weeks for 3 months, and then every 1 to 3 month thereafter, or as required by the doctor.
- Increase monitoring to weekly if ALT/AST >3 times ULN, until the problem is resolved.
- If ALT/AST is more than 5 times ULN, suspend treatment; continue to check LFTs every week until the problem is resolved.
-
Hypersensitivity reactions
- There have been cases of severe allergic reactions, including anaphylaxis.
- For severe reactions, suspend permanently and then handle as necessary.
-
Infections [US Boxed Warning]
- Patients who have received idelalisib treatment have experienced severe and sometimes fatal infections.
- Examine your body for signs and symptoms.
- If the infection is suspected, then Interrupt idelalisibFor grade 3 and higher infections
- There have been infections with single-agent idelalisib, rituximab and unapproved combinations therapies.
- Commonly reported infections are pneumonia, sepsis and febrile neutropenia.
- Before starting the medication with Idelalisib, it is important to treat any infection.
- Rarely have severe cases of cytomegalovirus and pneumocystis pneumonia (PCP), some even fatal, been reported.
- Provide PCP prophylaxis during idelalisib therapy (and even after discontinuation, if infection remains).
- If you are concerned about PCP infection, stop treatment immediately. Permanent discontinue treatment if the infection is confirmed.
- Patients with CMV infection are recommended to have their CMV levels checked regularly (clinical or laboratory).
- Stop taking idelalisib if you have a positive CMV PCR test or an antigen test. Wait until the infection is gone.
- Check for CMV activation every month if idelalisib has been restarted.
-
Pneumonitis: [US-Bound Warning]
- It is possible to get severe and/or fatal pneumonitis.
- Examine for symptoms such as pulmonary irritation and bilateral interstitial leakages.
- Therapy interruptions or discontinuations may be necessary.
- Interstitial infiltrates or organizing pneumonia are common clinical signs.
- It takes between 1 and 15 months for symptoms to begin.
- Stop treating if you experience symptoms like cough, dyspnea or hypoxia.
- If you are diagnosed with symptomatic pneumonia or organizing pneumonia, start the appropriate corticosteroids and discontinue idelalisib.
|
Alosetron |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. |
|
Apixaban |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apixaban. |
|
Benperidol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. |
|
Betamethasone (Ophthalmic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). |
|
Bictegravir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bictegravir. |
|
Bortezomib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Bosentan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. |
|
Brentuximab Vedotin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. |
|
Brinzolamide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. |
|
Budesonide (Nasal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). |
|
Budesonide (Oral Inhalation) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). |
|
Calcifediol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. |
|
Cannabidiol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. |
|
Cannabis |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. |
|
Chloramphenicol (Ophthalmic) |
May enhance the adverse/toxic effect of Myelosuppressive Agents. |
|
Cinacalcet |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. |
|
CloZAPine |
Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. |
|
CloZAPine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Coccidioides immitis Skin Test |
Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. |
|
Codeine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. |
|
Corticosteroids (Orally Inhaled) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. Exceptions: Beclomethasone (Oral Inhalation); Triamcinolone (Systemic). |
|
Corticosteroids (Systemic |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Systemic). Exceptions: MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE. |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of Idelalisib. |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Denosumab |
May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. |
|
DexAMETHasone (Ophthalmic |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Ophthalmic). |
|
Dienogest |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dienogest. |
|
Dofetilide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dofetilide. |
|
Doxercalciferol |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. |
|
Dronabinol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. |
|
Dutasteride |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. |
|
Enfortumab Vedotin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. |
|
Estrogen Derivatives |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. |
|
Evogliptin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. |
|
Fostamatinib |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. |
|
Galantamine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine. |
|
Ifosfamide |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. |
|
Imatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. |
|
Imidafenacin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. |
|
Lacosamide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide. |
|
Levamlodipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. |
|
Levobupivacaine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. |
|
Lumefantrine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. |
|
MedroxyPROGESTERone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of MedroxyPROGESTERone. |
|
Meperidine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Meperidine. |
|
Mesalamine |
May enhance the myelosuppressive effect of Myelosuppressive Agents. |
|
Naldemedine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. |
|
Nalfurafine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. |
|
Ocrelizumab |
May enhance the immunosuppressive effect of Immunosuppressants. |
|
Ospemifene |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. |
|
Oxybutynin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. |
|
Parecoxib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. |
|
Paricalcitol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. |
|
Pidotimod |
Immunosuppressants may diminish the therapeutic effect of Pidotimod. |
|
Polatuzumab Vedotin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. |
|
Pranlukast |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast. |
|
PrednisoLONE (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic). |
|
PredniSONE |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE. |
|
Promazine |
May enhance the myelosuppressive effect of Myelosuppressive Agents. |
|
Propafenone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Ramelteon |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. |
|
Repaglinide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may substantially increase the magnitude of increase in repaglinide exposure. |
|
Retapamulin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations. |
|
Rilpivirine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. |
|
RomiDEPsin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Sibutramine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sibutramine. |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Siponimod |
Immunosuppressants may enhance the immunosuppressive effect of Siponimod. |
|
Smallpox and Monkeypox Vaccine (Live) |
Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). |
|
SORAfenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. |
|
Tasimelteon |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. |
|
Tertomotide |
Immunosuppressants may diminish the therapeutic effect of Tertomotide. |
|
Tetrahydrocannabinol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. |
|
Tetrahydrocannabinol and Cannabidiol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
TraMADol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. |
|
Trastuzumab |
May enhance the neutropenic effect of Immunosuppressants. |
|
Vilanterol |
May increase the serum concentration of CYP3A4 Inhibitors (Strong). |
|
Vindesine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. |
|
Zolpidem |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. |
|
Risk Factor D (Consider therapy modification) |
|
|
Almotriptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. |
|
Baricitinib |
|
|
Bedaquiline |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit duration of concurrent use of bedaquiline with CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued use outweighs the possible risks. Monitor for toxic effects of bedaquiline. Exceptions discussed in separate monographs. |
|
Budesonide (Topical) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. |
|
Deferiprone |
Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. |
|
Delamanid |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Delamanid. Management: Increase ECG monitoring frequency if delamanid is combined with strong CYP3A4 inhibitors due to the risk for QTc interval prolongation. Continue frequent ECG assessments throughout full delamanid treatment period. Exceptions discussed separately. |
|
Drospirenone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Drospirenone. Management: Drospirenone use is contraindicated specifically when the strong CYP3A4 inhibitors atazanavir and cobicistat are administered concurrently. Caution should be used when drospirenone is coadministered with other strong CYP3A4 inhibitors. |
|
Echinacea |
May diminish the therapeutic effect of Immunosuppressants. |
|
Fingolimod |
Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). |
|
Iloperidone |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. |
|
Istradefylline |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. |
|
Leflunomide |
Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. |
|
Nivolumab |
Immunosuppressants may diminish the therapeutic effect of Nivolumab. |
|
PONATinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4 inhibitor. |
|
Roflumilast |
May enhance the immunosuppressive effect of Immunosuppressants. |
|
Sipuleucel-T |
Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. |
|
Thiotepa |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inhibitors. If concomitant use is unavoidable, monitor for adverse effects and decreased efficacy. |
|
Toremifene |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Management: Use of toremifene with strong CYP3A4 inhibitors should be avoided if possible. If coadministration is necessary, monitor for increased toremifene toxicities, including QTc interval prolongation. Exceptions are discussed in separate monograph. |
|
Vaccines (Inactivated) |
Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. |
|
Vilazodone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. |
|
Zuclopenthixol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. |
|
Risk Factor X (Avoid combination) |
|
|
Acalabrutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. |
|
Ado-Trastuzumab Emtansine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. |
|
Alfuzosin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. |
|
Aprepitant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. |
|
Astemizole |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Asunaprevir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. |
|
Avanafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil. |
|
Avapritinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. |
|
Axitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. |
|
Barnidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. |
|
BCG (Intravesical) |
Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). |
|
BCG (Intravesical) |
Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). |
|
Blonanserin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. |
|
Bosutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. |
|
Bromocriptine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. |
|
Budesonide (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). |
|
Cladribine |
May enhance the immunosuppressive effect of Immunosuppressants. |
|
Cladribine |
May enhance the myelosuppressive effect of Myelosuppressive Agents. |
|
Cobimetinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. |
|
Conivaptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. |
|
CYP3A4 Inducers (Strong) |
May decrease the serum concentration of Idelalisib. |
|
CYP3A4 Substrates (High risk with Inhibitors) |
Idelalisib may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Dabrafenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. |
|
Dapoxetine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. |
|
Dipyrone |
May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased |
|
Domperidone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Dronedarone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Eletriptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. |
|
Eplerenone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. |
|
Everolimus |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. |
|
Flibanserin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. |
|
Fluticasone (Nasal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). |
|
Fosaprepitant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. |
|
Halofantrine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Ibrutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. |
|
Isavuconazonium Sulfate |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Management: Combined use is considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this contraindication despite strongly inhibiting CYP3A4. |
|
Ivabradine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. |
|
Lapatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib adult dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. |
|
Lefamulin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. |
|
Lemborexant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lemborexant. |
|
Lercanidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. |
|
Lomitapide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. |
|
Lovastatin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. |
|
Lumateperone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. |
|
Lurasidone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. |
|
Macitentan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. |
|
Naloxegol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. |
|
Natalizumab |
Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. |
|
Neratinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. |
|
NiMODipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. |
|
Nisoldipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. |
|
Palbociclib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. |
|
Pimecrolimus |
May enhance the adverse/toxic effect of Immunosuppressants. |
|
Pimozide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. |
|
Radotinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. |
|
Ranolazine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. |
|
Red Yeast Rice |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. |
|
Regorafenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. |
|
Rupatadine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. |
|
Salmeterol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. |
|
Silodosin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. |
|
Simeprevir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. |
|
Simvastatin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. |
|
Sonidegib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. |
|
St John's Wort |
May decrease the serum concentration of Idelalisib. |
|
Suvorexant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. |
|
Tacrolimus (Topical) |
May enhance the adverse/toxic effect of Immunosuppressants. |
|
Tamsulosin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. |
|
Terfenadine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Ticagrelor |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. |
|
Tolvaptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. |
|
Trabectedin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. |
|
Triazolam |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. |
|
Ubrogepant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ubrogepant. |
|
Udenafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. |
|
Ulipristal |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity. |
|
Upadacitinib |
Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. |
|
Vaccines (Live) |
Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). |
|
VinCRIStine (Liposomal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). |
|
Vinflunine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. |
|
Vorapaxar |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. |
Monitoring parameters:
- For the first six months, complete blood counts with differential should be done at least once every two weeks, and weekly for patients with neutropenia (ANC >1,000/mm3) or as required by clinical practice.
- Liver function tests are done at baseline, every 2 weeks for 3 months, every 4 week for the next 3 and then every 1 to 3 month thereafter, or as required by the physician.
- Before beginning treatment for females with reproductive potential, it is important to conduct a pregnancy test
- Monitor for infection (including pneumonia, sepsis, PCP, CMV).
- Monitor for symptoms such as diarrhea/colitis or intestinal perforation, asthma, epilepsy, and allergic reactions.
- Pay attention.
How to administer Idelalisib (Zydelig)?
Oral:
- May be given with or without food. Swallow the tablets whole.
Missed doses:
- May give the missed dose if within 6 hours of usual dosing time.
- If >6 hours, skip the missed dose and resume treatment with the next scheduled dose.
Mechanism of action of Idelalisib (Zydelig):
- Idelalisib, a small-molecule inhibitor that is potent against the delta isoform phosphatidylinositol 3kinase (PI3Kd), is highly expressed in malignant lymphoid-B-cells.
- PI3Kd inhibition causes malignant tumor cells to die.
- Additionally, idelalisib inhibits many signaling pathways including CXCR4, B-cell receptor and CXCR5 signaling, which could play an important role in CLL pathophysiology.
Protein binding:
- ≥84%
Metabolism:
- Hepatic; primarily via aldehyde oxidase and CYP3A (to major metabolite GS563117); minor metabolism via UGT1A4
Half-life elimination:
- 8.2 hours
Time to peak:
- Median: 1.5 hours
Excretion:
- Feces (78%);
- urine (14%)
International Brand Names of Idelalisib:
- Zydelig
Idelalisib Brand Names in Pakistan:
No Brands Available in Pakistan.
.png)
